The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 23, 2015, Pages 7189-7194

  Elbaum Garfinkle, Shana ^a   Kim, Younghoon ^b   Szczepaniak, Krzysztof ^c,d,e   Chen, Carlos Chih Hsiung ^a   Eckmann, Christian R ^c,d   Myong, Sua ^b   Brangwynne, Clifford P ^a  

^a Princeton University   (United States)

^b University of Illinois at Urbana Champaign   (United States)

^c MAX PLANCK INSTITUTE OF MOLECULAR CELL BIOLOGY AND GENETICS   (Germany)

^d MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

^e Dresden International PhD Program   (Germany)

Author keywords

Intracellular phase transition; Intrinsically disordered proteins; Liquid droplets; RNA granules

Indexed keywords

CAENORHABDITIS ELEGANS PROTEIN; CAENORHABDITIS ELEGANS PROTEIN LAF 1; INTRINSICALLY DISORDERED PROTEIN; P GRANULE PROTEIN; UNCLASSIFIED DRUG; HELMINTH RNA; RNA HELICASE;

AMINO TERMINAL SEQUENCE; ARTICLE; CELL CYCLE PHASE; CELL ORGANELLE; CONTROLLED STUDY; EMBRYO; FLUIDIZATION; GENE SILENCING; IN VITRO STUDY; IN VIVO STUDY; MOLECULAR DYNAMICS; NONHUMAN; PHASE SEPARATION; PHASE TRANSITION; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN DEPLETION; PROTEIN LOCALIZATION; PROTEIN RNA BINDING; PROTEIN SECONDARY STRUCTURE; RNA BINDING; VISCOELASTICITY; ANIMAL; CAENORHABDITIS ELEGANS; CHEMISTRY; GENETICS; PHYSIOLOGY; VISCOSITY;

CAENORHABDITIS ELEGANS;

ANIMALS; CAENORHABDITIS ELEGANS; CAENORHABDITIS ELEGANS PROTEINS; RNA HELICASES; RNA, HELMINTH; VISCOSITY;

EID: 84930960021     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1504822112     Document Type: Article

References (43)

1. Anderson P, Kedersha N (2006) RNA granules. J Cell Biol 172(6):803-808.
2. Brangwynne CP, et al. (2009) Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324(5935):1729-1732.
3. Brangwynne CP, Mitchison TJ, Hyman AA (2011) Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proc Natl Acad Sci USA 108(11):4334-4339.
4. Wippich F, et al. (2013) Dual specificity kinase DYRK3 couples stress granule condensation/ dissolution to mTORC1 signaling. Cell 152(4):791-805.
5. Feric M, Brangwynne CP (2013) A nuclear F-actin scaffold stabilizes RNP droplets against gravity in large cells. Nat Cell Biol 15(10):1253-1259.
6. Hubstenberger A, Noble SL, Cameron C, Evans TC (2013) Translation repressors, an RNA helicase, and developmental cues control RNP phase transitions during early development. Dev Cell 27(2):161-173.
7. Weber SC, Brangwynne CP (2015) Inverse size scaling of the nucleolus by a concentration-dependent phase transition. Curr Biol 25(5):641-646.
8. Li P, et al. (2012) Phase transitions in the assembly of multivalent signalling proteins. Nature 483(7389):336-340.
9. Voronina E, Seydoux G, Sassone-Corsi P, Nagamori I (2011) RNA granules in germ cells. Cold Spring Harb Perspect Biol 3(12):3.
10. Lee CF, Brangwynne CP, Gharakhani J, Hyman AA, Jülicher F (2013) Spatial organization of the cell cytoplasm by position-dependent phase separation. Phys Rev Lett 111(8):088101.
11. Updike D, Strome S (2010) P granule assembly and function in Caenorhabditis elegans germ cells. J Androl 31(1):53-60.
12. Yarunin A, Harris RE, Ashe MP, Ashe HL (2011) Patterning of the Drosophila oocyte by a sequential translation repression program involving the d4EHP and Belle translational repressors. RNA Biol 8(5):904-912.
13. Beckham C, et al. (2008) The DEAD-box RNA helicase Ded1p affects and accumulates in Saccharomyces cerevisiae P-bodies. Mol Biol Cell 19(3):984-993.
14. Shih JW, et al. (2012) Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1 in stress granule assembly and stress response. Biochem J 441(1):119-129.
15. Uversky VN, Kuznetsova IM, Turoverov KK, Zaslavsky B (2015) Intrinsically disordered proteins as crucial constituents of cellular aqueous two phase systems and coacervates. FEBS Lett 589(1):15-22.
16. Kato M, et al. (2012) Cell-free formation of RNA granules: Low complexity sequence domains form dynamic fibers within hydrogels. Cell 149(4):753-767.
17. Han TW, et al. (2012) Cell-free formation of RNA granules: Bound RNAs identify features and components of cellular assemblies. Cell 149(4):768-779.
18. Decker CJ, Teixeira D, Parker R (2007) Edc3p and a glutamine/asparagine-rich domain of Lsm4p function in processing body assembly in Saccharomyces cerevisiae. J Cell Biol 179(3):437-449.
19. Weber SC, Brangwynne CP (2012) Getting RNA and protein in phase. Cell 149(6): 1188-1191.
20. Goodwin EB, Hofstra K, Hurney CA, Mango S, Kimble J (1997) A genetic pathway for regulation of tra-2 translation. Development 124(3):749-758.
21. Hubert A, Anderson P (2009) The C. elegans sex determination gene laf-1 encodes a putative DEAD-box RNA helicase. Dev Biol 330(2):358-367.
22. Asherie N (2004) Protein crystallization and phase diagrams. Methods 34(3):266-272.
23. Dill KA, Bromberg S (2011) Molecular Driving Forces: Statistical Thermodynamics in Biology, Chemistry, Physics, and Nanoscience (Garland Science, New York).
24. Debenedetti PG (1996) Metastable Liquids: Concepts and Principles (Princeton Univ Press, Princeton).
25. Brangwynne CP (2011) Soft active aggregates: Mechanics, dynamics and self-assembly of liquid-like intracellular protein bodies. Soft Matter 7(7):3052-3059.
26. Mason TG, Weitz DA (1995) Optical measurements of frequency-dependent linear viscoelastic moduli of complex fluids. Phys Rev Lett 74(7):1250-1253.
27. Larson RG (1999) The Structure and Rheology of Complex Fluids (Oxford Univ Press, New York).
28. Howard J (2001) Mechanics of Motor Proteins and the Cytoskeleton (Sinauer Associates, Sunderland, MA).
29. Aarts DG, Schmidt M, Lekkerkerker HN (2004) Direct visual observation of thermal capillary waves. Science 304(5672):847-850.
30. Roy R, Kozlov AG, Lohman TM, Ha T (2007) Dynamic structural rearrangements between DNA binding modes of E. coli SSB protein. J Mol Biol 369(5):1244-1257.
31. Xue B, Dunbrack RL, Williams RW, Dunker AK, Uversky VN (2010) PONDR-FIT: A metapredictor of intrinsically disordered amino acids. Biochim Biophys Acta 1804(4):996-1010.
32. Chen YH, Yang JT, Martinez HM (1972) Determination of the secondary structures of proteins by circular dichroism and optical rotatory dispersion. Biochemistry 11(22):4120-4131.
33. Dyson HJ, Wright PE (2005) Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 6(3):197-208.
34. Gallo CM, Wang JT, Motegi F, Seydoux G (2010) Cytoplasmic partitioning of P granule components is not required to specify the germline in C. elegans. Science 330(6011):1685-1689.
35. Paz-Gómez D, Villanueva-Chimal E, Navarro RE (2014) The DEAD Box RNA helicase VBH-1 is a new player in the stress response in C. elegans. PLoS ONE 9(5):e97924.
36. Sheth U, Pitt J, Dennis S, Priess JR (2010) Perinuclear P granules are the principal sites of mRNA export in adult C. elegans germ cells. Development 137(8):1305-1314.
37. Voronina E (2013) The diverse functions of germline P-granules in Caenorhabditis elegans. Mol Reprod Dev 80(8):624-631.
38. Hyman AA, Brangwynne CP (2011) Beyond stereospecificity: Liquids and mesoscale organization of cytoplasm. Dev Cell 21(1):14-16.
39. Ward JJ, Sodhi JS, McGuffin LJ, Buxton BF, Jones DT (2004) Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. J Mol Biol 337(3):635-645.
40. Toretsky JA, Wright PE (2014) Assemblages: Functional units formed by cellular phase separation. J Cell Biol 206(5):579-588.
41. Wang JT, et al. (2014) Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. elegans. eLife 3:e04591.
42. Nott TJ, et al. (2015) Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Mol Cell 57(5):936-947.
43. Thandapani P, O'Connor TR, Bailey TL, Richard S (2013) Defining the RGG/RG motif. Mol Cell 50(5):613-623.